Optogenetics — Treating Pain With Light

Optogenetics — Treating Pain With Light

Chronic pain research often spends time and money looking for new pain targets in order to develop more effective drug interventions. While this is time well spent, drug interventions can be decades in the making and often come with powerful and dangerous side effects. A growing field of research is looking for non-invasive, non-pharmaceutical ways to treat chronic pain, with a new focus: light. Can chronic pain be treated with light? Optogenetics is a field that has set out to answer that question and believes the answer is yes.

What is optogenetics?

Optogenetics is the use of light to control electrical activity in the brain. Understanding how the brain works is important to understand how optogenetics can control this activity.

Proteins produced by “opsin” genes help control electrical signals across cell membranes. These electrical signals are responsive to light and carry information and energy. The firing of neurons depends on if the ions crossing the cell membrane are positively or negatively charged. The more positively charged ions, the better chance the neuron will fire. Opsin genes regulate which ions cross the cell membrane.

These opsin genes can be controlled by changing the type of light they are exposed to.

There are two types of opsins:

Channelrhodopsin: Considered an “on” opsin. Blue light prompts channelrhodopsin to allow positive ions into the cell

Halorhodopsin: An “off” opsin that allows negative ions to enter the neuron when exposed to yellow light

While neither of these are present naturally in humans, researchers have placed these genes in mice to study how they can be controlled.

To activate these opsins, researchers insert a “light pipe” into the skull to direct a quick flash of light. They then study how these flashes have affected the neuronal activity.

In mice, researchers also used light applied outside the body to see how pain processing neurons would respond. They turned pain processing neurons on by shining a blue light through the floor of a mouse’s cage, causing pain in the mouse’s hind paw. To turn pain processing neurons off, they shone yellow light through the floor. Not only were the mice less sensitive to painful stimuli, but those mice in chronic pain were no longer overly sensitive to heat and painful touch.

What are the challenges of optogentics?

Optogenetics for chronic pain is a promising treatment that is not pharmaceutical and is non-invasive. As neither of these opsins are present in humans and humans are mobile, optogenetics for controlling chronic pain has two specific challenges:

Introducing opsins into the human body safely

Designing treatments that move with people

To meet the first challenge, researchers at Stanford have designed a way to introduce opsins into the body. Researchers used non-disease-causing virus as a vehicle to carry the opsins into the sciatic nerve of mice. The cells in the injected area then begin to make opsins. In theory, this could work for humans as well.

The second challenge lies in how to deliver treatment to chronic pain patients. An article published in Nature Biotechnology reports that a team of researchers has created a soft, implantable device that uses wireless radio power to deliver light to the spinal cord and peripheral nervous system.

Optogenetics for chronic pain

Optogenetics is often compared to the same types of deep brain stimulation that is used to treat Parkinson’s disease. While deep brain stimulation may work for some Parkinson’s patients, the way it works is unknown, and not all patients find relief. If optogenetics can use light to stimulate a consistent neuronal response, it could potentially replace highly invasive deep brain stimulation for those with Parkinson’s.

Brain stimulation as a medical treatment is not isolated to Parkinson’s disease and has also been used for chronic pain. There is a sense of urgency among researchers as the number of chronic pain sufferers swells right along with the opioid epidemic in the U.S.

Research by scientists at the Montreal Neurological Institute and Hospital of McGill University and the McGill University Health Centre carried out less invasive optogenetic research on mice with an eye to advancing this technology one step closer to humans.

Professor Philippe Séguéla, a researcher at the Montreal Neurological Institute and Hospital, conducted studies of optogenetics on mice with the goal of finding a better way to treat chronic pain. He noted:

“Chronic pain is an increasingly big problem clinically and for many years we’ve relied only on opiates. It’s hard to treat because of tolerance, making it necessary to increase dosages, which leads to serious side effects. Optogenetic therapy could be a highly effective way to relieve chronic pain while avoiding the side effects of traditional pain medication.”

The final word on optogenetics

There is no doubt that optogenetics holds promise for those with chronic pain, but there are many complications on the road to treatment. The ethics of injecting foreign genes into humans is questionable, even those who are consenting study participants.

Additionally, humans are not mice. They are highly mobile and come with a host of other considerations when it comes to treatments. Complicating factors in humans such as lifestyle and underlying medical conditions may not make this treatment as cut-and-dry as it sounds.

There also remains the question of how often treatments need to be administered. In animal studies, mice felt the effects of optogenetics as long as the gene was manipulated. Does this mean that humans will need to have a steady stream of light or receive many treatments, or will manipulating the genes result in permanent relief?

These questions and more are the focus of continuing research in this field. The history of optogenetics is still being made, and treatment with light may be a long time coming. If the promise of this non-invasive treatment holds true, it could bring relief to millions of chronic pain sufferers worldwide.